Changes in the disposition of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter in the central nervous system (CNS), have been postulated to occur in certain neurological and psychiatric disorders, though definitive proof is lacking due to an inability to measure this neurotransmitter in living systems. Preliminary experiments using a new assay technique have suggested that GABA is present in mammalian blood. Since GABA is primarily, if not entirely, stored in the CNS, the amount of amino acid in blood may reflect the activity of central GABAergic neurons and might be useful in monitoring this system in man and laboratory animals. The objective of this investigation is to verify the presence of this neurotransmitter in blood and to determine whether blood GABA derives primarily from the CNS. Using a radioreceptor technique, experiments will be undertaken with rat blood to demonstrate that the GABA-like substance already observed is indeed GABA by studying its physico-chemical properties. If it is GABA, the source of this blood GABA will be sought by injecting rats intraventricularly with 3H-GABA to determine whether this agent can be transported unchanged from CSF to blood. In addition, brain GABA levels will be manipulated to study the presence of a circulating GABA receptor agonist or antagonist, whose identity and neurobiological function could be explored. If the blood substanc is GABA, but does not originate in the CNS, the results may provide evidence for peripheral GAGAergic neurotransmission. If, however, the substance in blood is GABA derived from the CNS, this study would lead to the development of a rapid, simple and sensitive procedure for studying the activity of this CNS neurotransmitter in living organisms. Such a procedure could be clinically useful in diagnosing and treating CNS disfunctions resulting from a disorder in this transmitter system.